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However, patients with repaired TOF are at a risk of ventricular tachycardia (VT) and sudden cardiac death. Generally, reentry tachycardia observed around the surgical scar is a common mechanism underlying the development of VT in patients with repaired TOF.
On the other hand, catecholaminergic polymorphic VT (CPVT) is an inherited arrhythmia syndrome that presents with recurrent lethal ventricular tachyarrhythmia during exercise and acute emotions. Approximately half of the patients with CPVT exhibit a ryanodine receptor 2 mutation (RyR2). Patients with CPVT usually do not have congenital heart disease.
There are no reports of patients with TOF suffering from CPVT. Therefore, we aimed to present the first report of TOF with CPVT.
The patient was a 3-year-old boy. He was diagnosed with TOF and persistent left superior vena cava at birth. His cyanosis gradually progressed, and his physician started treatment with carteolol to avoid an anoxic spell. When he was 6 months old (Figure 1), his oxygen saturation decreased to 75%, and he underwent cardiac surgery (right ventricular outflow tract [RVOT] muscle resection, ventricular septal defect closure with a Dacron patch, repair of RVOT with a monocusp patch, and patent ductus arteriosus ligation). The patient required temporary pacing only for 7 days after surgery and was discharged 20 days after surgery. No VT was observed during the perioperative period. After the surgery, sinus bradycardia (heart rate, 65 beats/min), complete right bundle branch block, and residual pulmonary regurgitation (PR) were observed, which was followed by diuretic administration. He experienced 2 syncopal attacks during febrile illness. However, electrocardiography at the syncope episodes was not recorded. Then, he was suspected of having febrile convulsion.
At 3 years of age, while riding a tricycle, the patient suddenly collapsed. Because bystanders could not detect either a pulse or breathing, immediate resuscitation was performed. An automated external defibrillator was used, and his ventricular fibrillation (VF, Figure 2A ) changed to VT. The patient was transferred to the intensive care unit by an ambulance. At admission, bidirectional VT persisted (Figure 2B); as the initial treatment, a drip infusion of amiodarone and landiolol hydrochloride was administered, and deep sedation and therapeutic hypothermia were induced. VT ceased 2 days after admission, and sedation was stopped using an antiarrhythmic agent. However, multifocal premature ventricular contractions and bidirectional VT repeatedly appeared as a result of sympathetic nerve activation, manifesting with signs such as crying and vomiting. Lidocaine and amiodarone were ineffective in preventing and terminating bidirectional VT. However, flecainide was very effective in terminating bidirectional VT.
A resting electrocardiogram obtained in the pediatric ward revealed a complete right bundle branch block and sinus bradycardia (Figure 2C). An echocardiogram revealed normal left ventricular function, no residual ventricular septal defects, mild tricuspid regurgitation, and moderate PR. Cardiac magnetic resonance imaging revealed a PR ratio of 40.7%, right ventricle (RV) end-diastolic volume index of 106 mL/m2, and no late gadolinium enhancement in the ventricular wall. Additionally, cardiac catheterization showed no coronary artery stenosis, severe PR, or RV dilation (RV end-diastolic volume index, 125 mL/m2). We performed electrophysiological measurement to check for the occurrence of scar-related VT. Programmed electrical stimulation at the RV apex and RVOT did not induce any ventricular arrhythmias. Epinephrine and isoproterenol infusions reproducibly induced bidirectional VT. We initiated treatment with a beta-blocker and flecainide; however, the combination of these agents induced severe sinus bradycardia and QT prolongation, and bidirectional VT sometimes appeared under conditions of sympathetic nerve activation. We diagnosed him with CPVT because he developed bidirectional VT triggered by emotion, although he also had TOF. Because of critical sinus bradycardia and severe PR, RVOT re-repair was performed using a pulmonary valve conduit (CONTEGRA; Medtronic, Minneapolis, MN) and implantable cardioverter-defibrillator (ICD) implantation. An atrial lead was placed on the free wall of the right atrium. A ventricular lead was placed on the lateral side of the left ventricle. A distal shock coil was placed on the transverse sinus, and a proximal shock coil was placed in front of the RV. The generator was then inserted into the rectus abdominis muscle (Figure 3). VF was induced by a T-wave shock, and cardioversion from the ICD successfully terminated VF. The minimum atrial pacing rate was 80 beats/min, and the QT interval was normalized.
Genetic screening revealed a point mutation in the RyR2 gene, S2246L (c.6737 A>G). There were no mutations in KCNQ1, KCNH2, or SCN5A. Our clinical diagnosis of CPVT was supported by finding a known pathogenic variant of RyR2.
Based on these findings, treatment with the oral flecainide and nadolol was continued, and a limitation on exercise was prescribed. Although nonsustained VT sometimes appeared when the patient experienced emotional stress, ICD therapy has not been required. His parents and 2 older brothers had normal electrocardiograms, had no history of syncope or VT, and did not wish to undergo genetic testing.
This is the first report of TOF in a patient who was diagnosed with CPVT based on genetic screening.
We suspected CPVT because of certain characteristics, such as inappropriate bradycardia for age and catecholamine surge, including vomiting and crying, which consistently induced multifocal premature ventricular contractions and bidirectional VT; additionally, flecainide was effective in terminating VTs. S2246L, an RyR2 mutation carried by this patient, is known to cause CPVT.
Aborted cardiac arrest was an initial symptom in this patient; however, previous history of fever convulsions could be caused by polymorphic VTs. In accordance with previous reports, bidirectional VT was caused by catecholamine discharge in this patient and was suppressed by the beta-blocker or flecainide. The association between inherited long QT syndrome and congenital heart disease, especially TOF, has been reported previously.
reported that 11 cases of congenital heart disease were complicated by inherited long QT syndrome. Mutation of KCNH2 was observed in 2 cases of TOF, and 1 of these patients experienced torsades de pointes. Chiu and colleagues
reported that 10 of 12 patients with repaired TOF who experienced VT and implanted ICD had long QT gene mutation/polymorphisms, which was significantly higher than the occurrence in patients who did not experience VT. To date, however, no cases of CPVT coexisting with congenital cardiac disease have been described. This, then, is the first report of CPVT coexisting with TOF.
The ICD was implanted for secondary prevention. As the patient had pulmonary valve regurgitation and RV dilatation, we chose to implant the epicardial lead system at the same time as the open surgery. The implantation of the intravenous ICD system was difficult because of his small physique. The implantation of a subcutaneous ICD was not indicated because cardiac pacing was necessary for treating sick sinus syndrome. However, methods for ICD implantation with an epicardial lead system in children have not been established. The distal shock coil was implanted through the transverse sinus, and the proximal shock coil was placed on the front of the RV. This procedure was previously performed in a 7-year-old patient with long QT syndrome type 2 in our hospital.
reported that 8 of 145 patients with epicardial leads exhibited coronary compression. In our patient, cardiac catheterization was preformed 1 year after ICD implantation, and cardiac computed tomography was performed at the age of 10 years; coronary compression was not observed. The patient was followed up and checked for VT and cardiac strangulation.
We encountered a patient with TOF and CPVT. This is the first report of a patient with TOF who was diagnosed with CPVT through gene screening.
Key Teaching Points
This is the first report of a patient with tetralogy of Fallot presenting with catecholaminergic polymorphic ventricular tachycardia (VT).
Although re-entrant VT is common in patients with tetralogy of Fallot after an intracardiac repair, comorbidity of inherited arrhythmias should be considered when polymorphic VT occurs in young patients.
Bradycardia may progress and promote heart failure when antiarrhythmic drugs are used in patients with a congenital heart disease and inherited arrhythmias. Maintaining appropriate heart rate with an implantable device can improve heart failure.
The genetic analysis for the CPVT diagnosis was conducted by Dr Takeshi Aiba of the National Cardiovascular Center.
Funding Sources: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Disclosures: Takahiro Eitoku and Shingo Kasahara declare no conflicts of interest associated with this article. Nobuhiro Nishii and Hiroshi Morita are affiliated with a department endowed by Japan Medtronic, Inc.